Question
Enumerate the second generation fluoroquinolones. What is their mechanism of action. What are the adverse effects produced by them. (2+2+2)
Answer
Second generation fluoroquinolones: Ciprofloxacin, Ofloxacin, Norfloxacin — good Gram-negative coverage including Pseudomonas, limited Gram-positive/atypical activity.
Mechanism of action Fluoroquinolones inhibit two bacterial type II topoisomerase enzymes essential for DNA replication: DNA gyrase, which introduces negative supercoils ahead of the replication fork, and topoisomerase IV, which separates interlinked daughter DNA circles after replication. In Gram-negative organisms, DNA gyrase is generally the primary target. Blocking these enzymes prevents DNA unwinding/religation, causing accumulated double-strand breaks and bactericidal cell death.
Adverse effects Tendinopathy and tendon rupture (particularly Achilles tendon, more common over age 60 or with concurrent corticosteroids), cartilage damage in developing joints (traditional contraindication in children/pregnancy), QT prolongation, CNS effects (headache, dizziness, lowered seizure threshold — worsened by concurrent NSAIDs), peripheral neuropathy (can be irreversible), photosensitivity.